Microdialysis probe technology provides access to tissue interstitium for either sampling of diffusible tissue constituents or delivery of bioactive substances. However, the relationship of the probe perfusate concentrations to their tissue counterparts is a complex function of solute molecular weight, solute physicochemical properties, tissue properties, probe membrane properties, probe geometry and perfusion rate, and the trauma of probe insertion into the tissue. These dependencies are being studied in order to improve the quantitative usefulness of the technology. The focus of applications is the brain in connection with diseases such as Parkinson's, AIDS and alcoholism. Endogenous solutes of interest include cyclic adenosine monophosphate (cyclic AMP) and dopamine. Exogenous substances employed as marker solutes or pharmacological agents are sucrose, acetaminophen, AZT, and ethanol. Mathematical modeling is being used to describe solute transport within the probe and in surrounding medium. Validation experiments in animals (usually rats) involve quantitative auto-radiography, histology, and chemical assay of tissue surrounding the probe, as well as measurement of probe perfusate concentrations.